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Design, synthesis, structure, in vitro cytotoxic activity evaluation and docking studies on target enzyme GSK-3β of new indirubin-3'-oxime derivatives

Authors :
Do Huu Nghi
Nguyen Huu Thuan Anh
Luu Van Chinh
Ngo Thi Lan
Long Giang Bach
Tran Quoc Toan
Nguyen Thi Mai
Hoang Duc Quang
To Dao Cuong
Nguyen Manh Cuong
Vuong Van Truong
Pham Minh Quan
Nguyen Trong Dan
Source :
Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Publication Year :
2020

Abstract

The addition of chalcone and amine components into indirubin-3′-oxime resulted in 15 new derivatives with high yields. Structures of new derivatives were also elucidated through 1D, 2D-NMR and HR-MS(ESI) spectra and X-ray crystallography. All designed compounds were screened for cytotoxic activity against four human cancer cell lines (HepG2, LU-1, SW480 and HL-60) and one human normal kidney cell line (HEK-293). Compound 6f exhibited the most marked cytotoxicity meanwhile cytotoxicity of compounds 6e, 6h and 6l was more profound toward cancer cell lines than toward normal cell. These new derivatives were further analyzed via molecular docking studies on GSK-3β enzyme. Docking analysis shows that most of the derivatives exhibited potential inhibition activity against GSK-3β with characteristic interacting residues in the binding site. The fast pulling of ligand scheme was then employed to refine the binding affinity and mechanism between ligands and GSK-3β enzyme. The computational results are expected to contribute to predicting enzyme target of the trial inhibitors and their possible interaction, from which the design of new cytotoxic agents could be created in the future.

Details

ISSN :
20452322
Volume :
10
Issue :
1
Database :
OpenAIRE
Journal :
Scientific reports
Accession number :
edsair.doi.dedup.....5649e27fbb2e3248f9ffd7a0e91265b9